Advertisement

Leukocytes and organ-nonspecific autoantibodies in schizophrenics and their siblings: markers of vulnerability or disease?

      This paper is only available as a PDF. To read, Please Download here.
      To determine whether leukocyte counts and organ-nonspecific autoantibodies mark familial vulnerability for schizophrenia and/or the disease itself, we examined 92 patients with schizophrenia and 94 unrelated, demographically balanced, healthy individuals. In addition, for 19 of the probands, one of their nonschizophrenic, full siblings also was recruited. At the time of the blood draw, most probands (87%) had been free of medications for a minimum of 2 weeks and about half were neuroleptic-naive, first-episode patients. Results indicate that a relative lymphopenia in the context of a relative granulocytosis appears to mark familial vulnerability for schizophrenia, whereas an absolute monocytosis appears to mark spectrum manifestations of the clinical phenotype. The former observation is consistent with the hypothesis that the etiology of schizophrenia is immunologically mediated, whereas the latter is consistent with emerging evidence that an inflammatory process is associated with the expression of the disorder. Neither antinuclear antibody nor rheumatoid factor emerged as liability or disease markers.

      Key Words

      References

        • Achiron A
        • Noy S
        • Pras E
        • Lereya J
        • Hermesh H
        • Laor N
        T-cel subsets in acute psychotic schizophrenic patients.
        Biol Psychiatry. 1994; 35: 27-31
        • Asano S
        • Okano A
        • Ozawa K
        • et al.
        In vivo effects of human interlukin-6 in primates: Stimulated production of platelets.
        Blood. 1990; 75: 1602-1605
        • Bach JF
        Insulin-dependent diabetes mellitus as an autoimmune disease.
        Endocrine Rev. 1994; 15: 516-542
        • Caldwell CL
        • Irwin M
        • Lohr J
        Reduced natural killer cell cytotoxicity in depresion but not in schizophrenia.
        Biol Psychiatry. 1991; 30: 1131-1138
        • Cannon Td
        • MArco E
        Structural brain abnormalities as indicators of vulnerability to schizophrenia.
        Schizophr Bull. 1994; 20: 89-102
        • Cannon TD
        • Eyler Zorrilla L
        • Shtasel D
        • et al.
        Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers.
        Arch Gen Psychiatry. 1994; 51: 651-661
        • Canoso RT
        • de Oliveira RM
        Characterization and antigenic specificity of chlorpromazine-induced antinuclear antibodies.
        J Lab Clin Med. 1986; 108: 213-216
        • Canoso RT
        • Sise HS
        Chlorpromazine-induced lupus anticoagulant and associated immunologic abnormalities.
        Am J Hematol. 1982; 13: 121-129
        • Canoso RT
        • de Oliveira RM
        • Nixon RA
        Neurolepticassociated autoantibodies: A prevalence study.
        Biol Psychiatry. 1990; 27: 863-870
        • Chengappa KN
        • Carpenter AB
        • Keshavan MS
        • et al.
        Elevated IGG and IGM anticardiolipin antibodies in a subgroup of medicated and unmedicated schizophrenic patients.
        Biol Psychiatry. 1991; 30: 731-735
        • Coffey CE
        • Sullivan JL
        • Rice JR
        T lymphocytes in schizophrenia.
        Biol Psychiatry. 1983; 18: 113-119
        • Dameshek W
        The white blood cells in dementia praecox and dementia paralytica.
        Arch Neurol Psychiatry. 1930; 24: 855
        • de Leon J
        • Dadvand M
        • Canuso C
        • White AO
        • Stanilla JK
        • Simpson GM
        Schizophrenia and smoking: An epidemiological survey in a state hospital.
        Am J Psychiatry. 1995; 152: 453-455
        • DeLisi LE
        • Wyatt RJ
        Abnormal immune regulation in schizophrenic patients.
        Psychopharmacol Bull. 1982; 18: 158-163
        • DeLisi LE
        • Goodman S
        • Neckers LM
        • Wyatt RJ
        An analysis of lymphocyte subpopulations in schizophrenic patients.
        Biol Psychiatry. 1982; 17: 1003-1009
        • DeLisi LE
        • Goldin LR
        • Gershon ES
        Studies of biological factors associated with the inheritance of schizophrenia: A selective review.
        J Psychiatr Res. 1987; 21: 507-513
        • Diebold K
        Leukocyte count in manics, endogenous depressives, schizophrenics and neurotics.
        Psychiatria Clinica. 1976; 9: 230-235
        • Eyler Zorrilla LT
        • Cannon TD
        Structural brain abnormalities in schizophrenia: Distribution, etiology, and implications.
        in: Mednick S Neural Development in Schizophrenia: Theory and Research. Plenum Press, New York1995: 57-69
        • Fessel WJ
        Disturbed serum proteins in chronic psychosis.
        Arch Gen Psychiatry. 1961; 4: 154-159
        • Fishman P
        • Sredni P
        • Djaldetti M
        Recent advances in interleukin-3 research: A review.
        Isr J Med Sci. 1990; 26: 414-419
        • Ganguli R
        • Rabin BS
        Cd5 positive b-lymphocytes in schizophrenia: No alteration in numbers or percentage as compared with control subjects.
        Psychiatry Res. 1993; 48: 69-78
        • Ganguli R
        • Brar JS
        • Solomon W
        • Chengappa KN
        • Rabin BS
        Altered interleukin-2 production in schizophrenia: Association between clinical state and autoantibody production.
        Psychiatry Res. 1992; 44: 113-123
        • Ganguli R
        • Rabin BS
        • Brar JS
        Antinuclear and gastric parietal cell autoantibodies in schizophrenic patients.
        Biol Psychiatry. 1992; 32: 735-738
        • Ganguli R
        • Brar JS
        • Chengappa KNR
        • Yang ZW
        • Nimgaonkar VL
        • Rabin BS
        Autoimmunity in schizophrenia: A review of recent findings.
        Ann Med. 1993; 25: 489-496
        • Ganguli R
        • Yang Z
        • Shurin G
        • et al.
        Serum interleukin-6 concentration in schizophrenia: Elevation associated with duration of illness.
        Psychiatry Res. 1994; 51: 1-10
        • Gottfries CG
        • Gottfries I
        Antinuclear factors in relation to age, sex, mental disease and treatment with phenothiazines.
        Acta Psychiatr Scand. 1974; 255 (suppl): 193-201
        • Harley JB
        • Sheldon P
        • Neas B
        • et al.
        Systemic lupus erythematosus: Considerations for a genetic approach.
        J Invest Dermatol. 1994; 103: 144S-149S
        • Herbert TB
        • Cohen S
        Depression and immunity: A meta-analytic review.
        Psychol Bull. 1993; 113: 472-486
        • Hirata-Hibi M
        • Hayashi K
        The anatomy of the Plymphocyte.
        Schizophr Res. 1993; 8: 257-262
        • Irwin M
        • Segal DS
        • Hauger RL
        • Smith TL
        Individual behavioral and neuroendocrine differences in responsiveness to audiogenic stress.
        Pharmacol Biochem Behav. 1989; 32: 913-917
        • Johnstone E
        • Whaley K
        Antinuclear antibodies in psychiatric illness: Their relationship to diagnosis and drug treatment.
        Br Med J. 1975; 2: 724-725
        • Katila H
        • Appelberg B
        • Hurme M
        • Rimon R
        Plasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders.
        Schizophr Res. 1994; 12: 29-34
        • Kronfol Z
        • House JD
        Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls.
        Acta Psychiatr Scand. 1989; 80: 142-147
        • Kronfol Z
        • Turner R
        • Nasrallah H
        • Winokur G
        Leukocyte regulation in depression and schizophrenia.
        Psychiatry Res. 1984; 13: 13-18
        • Kronfol Z
        • Turner R
        • House JD
        • Winokur G
        Elevated blood neutrophil concentration in mania.
        J Clin Psychiatry. 1986; 47: 63-65
        • Lohr JB
        • Flynn K
        Smoking and schizophrenia.
        Schizophr Res. 1992; 8: 93-102
        • Loranger AW
        • Susman VL
        • Oldham JM
        • Russakoff LM
        The Personality Disorder Examination: A preliminary report.
        J Personality Disord. 1987; 1: 1-13
        • Maes M
        • Van der Planken M
        • Stevens WJ
        • et al.
        Leukocytosis, monocytosis and neutrophilia: Hallmarks of severe depression.
        J Psychiat Res. 1992; 26: 125-134
        • Maes M
        • Meltzer HY
        • Bosmans E
        Immune-inflammatory markers in schizophrenia: Comparison to normal controls and effects of clozapine.
        Acta Psychiatr Scand. 1994; 89: 346-351
        • Maes M
        • Stevens W
        • Scharpe S
        • et al.
        Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6 and soluble interleukin-2 and -6 receptor concentrations in normal volunteers.
        Experientia. 1994; 50: 821-829
        • Masserini C
        • Vita A
        • Basile R
        • et al.
        Lymphocyte subsets in schizophrenic disorders. Relationship with clinical, neuromorphological and treatment variables.
        Schizophr Res. 1990; 3: 269-275
        • Milhorat AT
        • Small SM
        • Diethelm O
        Leukocytosis during various emotional states.
        Arch Neurol Psychiatry. 1942; 47: 779
        • Moreland LW
        • Koopman WJ
        Infection as a cause of arthritis.
        Curr Opin Rheumatol. 1991; 3: 639-649
        • Nyland H
        • Naess A
        • Lunde H
        Lymphocyte subpopulations in peripheral blood from schizophrenic patients.
        Acta Psychiatr Scand. 1980; 61: 313-318
        • Osgood EE
        • Brownlee IE
        • Osgood MW
        • Ellis DM
        • Cohen W
        Total, differential and absolute leukocyte counts and sedimentation rates determined for healthy persons nineteen years of age and over.
        Arch Int Med. 1939; 64: 105
        • Panitch HS
        Influence of infection on exacerbations of multiple sclerosis.
        Ann Neurol. 1994; 36 (suppl): S25-S28
        • Rapaport MH
        • Torrey EF
        • McAllister CG
        • Nelson DL
        • Pickar D
        • Paul SM
        Increased serum-soluble interleukin-2 receptors in schizophrenic monozygotic twins.
        Eur Arch Psychiatry Clin Neurosci. 1993; 243: 7-10
        • Reveley AM
        • Reveley MA
        • Clifford CA
        • Murray RM
        Cerebral ventricular size in twins discordant for schizophrenia.
        Lancet. 1982; i: 540-541
        • Sasaki I
        • Nanko S
        • Fukuda R
        • Kawate T
        • Kunugi H
        • Kazamatsuri H
        Changes of immunological functions after acute exacerbation in schizophrenia.
        Biol Psychiatry. 1994; 35: 173-178
        • SAS Institute
        SAS/STAT User's Guide. Author, New York1988
        • Shintani F
        • Kanba S
        • Maruo N
        • et al.
        Serum interleukin-6 in schizophrenic patients.
        Life Sci. 1991; 49: 661-664
        • Shtasel DL
        • Gur RE
        • Mozley PD
        • et al.
        Volunteers for biomedical research. Recruitment and screening of normal controls.
        Arch Gen Psych. 1991; 48: 1022-1025
        • Sirota P
        • Firer M
        • Schildi K
        • et al.
        Increased anti-Sm antibodies in schizophrenic patients and their families.
        Prog Neuro Psychopharmacol Biol Psychiatry. 1993; 17: 793-800
        • Sirota P
        • Firer MA
        • Schild K
        • et al.
        Autoantibodies to DNA in multicase families with schizophrenia.
        Biol Psychiatry. 1993; 33: 450-455
        • Sirota P
        • Schild K
        • Elizur A
        • Dialdetti M
        • Fishman P
        Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients.
        Prog Neuro Psychopharmacol. 1995; 19: 7583
        • Spitzer RL
        • Williams JB
        • Gibbon M
        Instruction Manual for the Structured Clinical Interview for DSM-III-R (SCID).
        Biometrics Research Department, New York State Psychiatric Institute, Cary, NC1987
        • Spitzer RL
        • Williams JB
        • Gibbons M
        • First MB
        Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II).
        Biometrics Research Department, New York State Psychiatric Institute, New York1987
        • Spring BJ
        • Zubin J
        Attention and information processing as indicators of vulnerability to schizophrenic episodes.
        in: Wynne LC Cromwell RL Matthysse S The Nature of Schizophrenia: Approaches to Research and Treatment. Wiley, New York1978: 366-375
        • Tsuang MT
        • Lyons MJ
        • Faraone SV
        Heterogeneity of schizophrenia. Conceptual models and analytic strategies.
        Br J Psychiatry. 1990; 156: 17-26
        • Ulich TR
        • del Castillo J
        • Busser K
        • Guo KZ
        • Yin SM
        Acute in vivo effects of IL-3 alone and in combination with IL-6 on the blood cells of the circulation and bone marrow.
        Am J Pathol. 1989; 135: 663-670
        • Ulich TR
        • del Castillo J
        • Guo K
        In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBC's and WBC's.
        Blood. 1989; 73: 108110
        • Ulich TR
        • Guo KZ
        • Remick D
        • del Castillo J
        • Yin S
        Endotoxin-induced cytokine gene expression in vivo: III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6.
        Immunol. 1991; 146: 2316-2323
        • Villemain F
        • Magnin M
        • Feuillet FMN
        • Zarifian E
        • Loo H
        • Bach JF
        Anti-histone antibodies in schizophrenia and affective disorders.
        Psychiatry Res. 1988; 24: 53-60
        • Villemain F
        • Chatenoud L
        • Galinowski A
        • et al.
        Aberrant T cell-mediated immunity in untreated schizophrenic patients: Deficient interleukin-2 production.
        Am J Psychiatry. 1989; 146: 609-616
        • von Brauchitsch H
        Antinuclear factor in psychiatric disorders.
        Am J Psychiatry. 1972; 128: 1552-1554
        • Weinberger DR
        • Delisi LE
        • Neophytides AN
        • Wyatt RJ
        Familial aspects of CT scan abnormalities in chronic schizophrenic patients.
        Psychiatry Res. 1981; 4: 65-71
        • Winokur G
        • Tsuang M
        Paranoid versus nonparanoid schizophrenia: Definition and association.
        in: Perris C Struwe G Jannson G Proceedings, Third World Congress of Biological Psychiatry. Elsevier/North-Holland, New York1981
        • Xu HM
        • Wei J
        • Hemmings GP
        Changes of plasma concentrations of interleukin-1 alpha and interleukin-6 with neuroleptic treatment for schizophrenia.
        Br J Psychiatry. 1994; 164: 251-253
        • Yannitsi SG
        • Manoussakis MN
        • Mavridis AK
        • et al.
        Factors related to the presence of autoantibodies in patients with chronic mental disorders.
        Biol Psychiatry. 1990; 27: 747-756
        • Zarrabi MH
        • Zucker S
        • Miller F
        • et al.
        Immunologic and coagulation disorders in chlorpromazine-treated patients.
        Ann Int Med. 1979; 91: 194-199